Mallory Hoffman, MD - 2024 Fetal Care Center Navigating Perinatal Care for Trisomy 13 & 18

I'm gonna go ahead now, uh, as we kind of use that interlude to talk next with Dr. Hoffman about uh prenatal care and what we're learning so far um and management options. Uh, Dr. Hoffman is one of the maternal fetal medicine specialists at Cincinnati Children's Fetal Care Center. Uh, she initially did her training at, uh, Cincinnati and then did her fellowship at UT Houston before she came back to Cincinnati. Um, and she's gonna talk to us about the prenatal care. Um, thank you. Um, so when we first meet with the family, when they come to us with either a confirmed diagnosis or a suspected diagnosis, we go over all of the imaging studies because, um, there's a wide variety in what types of differences we'll see in babies who have a diagnosis or a suspected diagnosis of trisomy 13 and trisomy 18. So the first thing that we want to do is go over all of the imaging studies and review what we see with the families and what types of issues we expect their baby to encounter during the pregnancy and after delivery. Sometimes we have that genetic diagnosis either because they have ultrasound findings consistent with what we see on their non-invasive prenatal screening or they've already had an amniocentesis before they come to us. But sometimes we're talking to the families after They've had, um, only an ultrasound, but have multiple findings that are concerning for, um, a diagnosis of trisomy 13 or trisomy 18. Um, so the goal of our meetings is to really get a feel for what, uh, types of interventions can be offered after delivery and what makes the most sense for that family. So while it's common to have multiple structural differences, Sometimes we do have babies that um really don't have any of the bigger features and have more soft markers or smaller features and may not need a surgery initially after delivery. So while we can also talk about um surgical procedures or interventions that are available for specific individual, Anomalies like a cardiac anomaly or aqueductal stenosis. The goal of the meeting um with the family and with all of the subspecialists is to identify their goals of care for the pregnancy and how we can best support them. So, there are a number of different options that a number of different choices that families can make um regarding their pregnancy. So some families choose to interrupt their pregnancy or have a pregnancy termination. So, while that is an option that is um presented to families, it's certainly not something that um they're hearing from us is you should do this. It's something that's presented as an option along with all of the other options, um, with comfort care and more aggressive care. So some families, after going over the imaging studies and meeting with the specialists and hearing some of that data that Doctor Suar just presented, decide that that's not a path that they feel comfortable continuing with their pregnancy. Um, and so they will choose to interrupt the pregnancy. Other families make a decision to continue the pregnancy. And decide that they do want to pursue some of the more aggressive interventions that are available after delivery, and some families choose more of what we consider the comfort care approach with a focus on um maximizing the time that the baby is spending with the family. In the room with the family, um, and keeping baby comfortable and doing memory making. And so our, um, perinatal, uh, palliative care team is, um, excellent at helping families choosing either comfort care or more of an aggressive care path, make decisions about Um, what types of memory making is important, who they want to meet the baby after delivery, who they want in the room. Um, so in patients who are continuing their pregnancy, we have a number of considerations that we need to, um, Uh, take into consideration when we're talking about their care. So one is that all pregnant moms still need regular routine prenatal care. So we do still recommend that um they get their diabetes screening, that they're having um regular Blood tests, um, to make sure that they're not developing anemia or developing antibodies during their pregnancy and having a check-in with their OB, um, to keep an eye on their blood pressure and just everything that we, um, also routinely monitor in, um, any other pregnancy as well. Um, as Doctor Swar said, 13% of patients with trisomy 13 or trisomy 18 in these studies had preterm labor. Um, that's not all that different from the general population. Um, about 10% of pregnancies have preterm, uh, deliveries. Um, and so the rate of preterm labor in this population isn't significantly different. One of the things that may contribute to the slightly higher um incidence of preterm labor in this population is increased amniotic fluid. So increased amniotic fluid can happen for a number of reasons. Sometimes there can be differences in the way the baby's GI system has formed, if there's a blockage, um, in their intestines, um, if they're not able to swallow the amniotic fluid, then it builds up. And that increased, um, stretch on the uterus, that increased fluid can increase the chances of the water breaking earlier of the mom going into labor earlier. Um, it's also more common to have a condition called micrognathia or a small jaw, and that can prevent the baby from being able to swallow the fluid as well. Sometimes, even if there's no structural cause of not being able to swallow fluid, um, we could be also suspicious of a brain difference. And so if the baby's brain is not sending the signals to do the swallowing that we typically expect to see in a fetus, then, um, even though the baby is continuing to urinate, they may not be swallowing the fluid. And so that can also lead to the fluid building up. So even when we're seeing somebody in their 2nd trimester, early 3rd trimester, I always talk to those families about how polyhydramnios may develop later in the pregnancy just because it is such a common finding. If the amniotic fluid around the baby increases, um, quite a bit, sometimes, uh, moms may need a procedure called an amnio reduction, which is when we have to drain some of the fluid that's, um, around the baby, and we do that. Using a 20 gauge spinal needle just like with an amniocentesis, but instead of taking a small sample for genetic testing, we're taking at times several liters of amniotic fluid off, um, in order to take that pressure off of, um, the extra stretch that's on the uterus. So any procedure does increase the risk of complications like bleeding, the water could break, um, it can trigger labor, but the purpose of the procedure is to take that pressure off and hopefully prolong the pregnancy as much as possible. Um, some families who haven't had genetic testing earlier in the pregnancy will choose to have genetic testing done if an amnio reduction is needed, um, which is also a reasonable option. Um, so we have to keep a very close eye on the amniotic fluid around the baby during the pregnancy as well as their growth. So how frequently we do ultrasounds and how frequently and what types of testing we do during the pregnancy is really driven by the family and what types of um care they're hoping to have after delivery. Some families, when they decide that they want more of a comfort care approach, Um, find it stressful to come in for more ultrasounds and don't want as much, um, monitoring, um, because it's anxiety provoking for them. For instance, if when they come for an ultrasound, they can see some of these anomalies, and so we've had families say that they want to try to limit the ultrasounds that they get, and that's OK too. At a minimum, if patients want to minimize testing, I recommend at least a growth scan every month so that we can keep an eye on how the um fetus is developing and make sure that there aren't any other things coming up like increased head size that could prevent the mom from being able to have a vaginal delivery, um, as once labor happens or once we get to full term. So at a minimum, I recommend that we have at least a monthly growth scan. But, um, if patients want more close monitoring, then oftentimes we'll do growth scans every 2 to 3 weeks after the 3rd trimester, um, because growth abnormalities are something that are very common with the diagnosis of trisomy 13 and trisomy 18. Sometimes there can be differences that don't show up until later, until the 3rd trimester. And so, the findings that we see at a 20-week anatomy scan, we may see additional findings later in the pregnancy, and we would also always incorporate those differences into our counseling of what type of care we think the baby may need after delivery. Um, antenatal testing or non-stress tests is also something that is driven by, um, really the family's wishes. So the risk for a stillbirth once we get to the third trimester is about 13%. So, um, when I was in medical school and residency, initially, I had always thought that the teaching was that trisomy 13 and trisomy 18 was a lethal diagnosis. And so, the thoughts of doing non-stress tests to try to prevent a stillbirth weren't the same as, as I've learned a little bit more about um trisomy 13 and trisomy 18 and how some of the practices Um, have changed in recent years. So, um, the risk of stillbirth, while it's still quite a bit higher than it was, um, Uh, the, uh, the risk of stillbirth is still quite a bit higher than it is in, um, patients who don't have a genetic difference. Um, it's certainly far from all, most of these kids are born stillborn. Excuse me. So, about a 13% risk of stillbirth is there. So non-stress tests, the purpose of those is to make sure that the baby is um happy and healthy on the inside and that um there isn't an increased risk for stillbirth in the coming days. So, with a non-stress test, we place the mom, um, the baby on the monitor like we would during labor. We watch the heartbeat and we watch for contractions. Um, as we're watching, um, for contractions, sometimes if the mom has increased amniotic fluid, we may see more contractions that could prompt a discussion of should we be considering an amnio reduction if there's also polyhydramnios. Um, but also watching the heart rate to make sure that we're not having dips in the heart rate or anything that should prompt Watching for a longer period of time, admitting to the hospital, or potentially even an earlier delivery. Um, some families, uh, want to prioritize vaginal delivery. Some families, the most important thing is a live birth, and so we always incorporate the families into the discussion of how frequently do they want to do the non-stress tests, um, and if they're wanting to do them at all. So, um, If families do want to do non-stress tests, we typically recommend 2 times a week. Um, it's not perfect for preventing stillbirth, but, um, ideally helps us pick up babies that are in distress earlier so that we can prioritize, um, a live birth or an earlier delivery if we're seeing testing that's not reassuring. Um, When it comes time to scheduling a delivery, there's a lot of factors that go into that, the health of the mom, are we having elevated blood pressures or any other medical conditions that need to be taken into consideration, um, as well as the growth of the baby. It is common for babies with trisomy 13 or trisomy 18 to have growth restriction. And so, um, if we do have growth restriction, depending on the degree of growth restriction or if there's any, um, blood flow abnormalities, any Doppler abnormalities noticed during the pregnancy, that could, um, prompt a different timing of delivery, as well as if there's increased amniotic fluid. So when it does come time for delivery, We also include the family in the discussion about how delivery happens. Sometimes, um, there can be an uh another reason to need a C-section, for instance, the baby's head size is too big to fit vaginally, and in that situation, a C-section would be needed even with a completely comfort care approach. Sometimes moms have had cesarean sections in the past and want to have a repeat C-section. And so in those situations, um, that is something that we would honor those wishes. But we've also had moms who have had cesarean sections in the past who want to prioritize having a vaginal delivery. And so if um the patients are choosing vaginal delivery, then we can um discuss as even further what type of monitoring they want during delivery. Some families want just like with uh uh an induction that we were doing in a baby that didn't have any structural differences or genetic differences, where we put you on the monitor and you're on the monitor the entire time. And if we see dips in the heart rate, we go for a cesarean section. But other families want to prioritize having a vaginal delivery and have more limited fetal monitoring. Um, there is always a risk of having a stillbirth during the induction process. Um, and for some families, they'll say, if we have a live birth, then we want to see what, um, types of interventions might help baby after delivery. But other families, um, prefer to have, um, more monitoring, and if we're seeing dips in the heart rate, then convert to a cesarean section. So the chance for a C-section is higher with a diagnosis of trisomy 13 and trisomy 18. Um, as Doctor Swar also presented, the chance for a cesarean section was 48%. 48% of these moms, or almost half of them, had a cesarean section for delivery in our area. Um, in the general population in the United States, 32% or about a third of moms have a cesarean section of our 32% of our births in the US are cesarean section. So the chance for a cesarean section is higher. Some of that may be related to having um babies that are smaller, a placenta that doesn't tolerate labor as well, or just structural differences with the baby that increase the risk of a cesarean section, such as umphalocele or an enlarged head size. All right. Um, I think we can go to the Q&A for this session. Thanks, Doctor Hoffman. Um, can you talk a little bit about what you've experienced, uh, as we live in a, um, area of changing legislation and what type of different, um, impressions or concerns families have had as they've been coming in with this diagnosis? Yeah, so I'll start by saying I don't think anybody knows what they would do until they were in that situation. And we hear from families all the time, interrupting a pregnancy is not something that we ever would have considered, but knowing. What this baby will be up against, or, and there's also situations that it increases the risk for the mom as well. And so I don't think anybody knows what they would do until they were in that situation. But um, I think that the patients that we see here are more selected towards people who are interested in hearing about the interventions that we can offer after delivery. So I think my experience would be quite different than somebody who is a maternal fetal medicine physician who doesn't work at a fetal care center, um, where they may say more of our patients are deciding to terminate. Um, but certainly, the options that are available for patients are quite different depending on where they live. Um, And financial limitations can also keep people from being able to travel out of state for a termination, if that's something that they were interested in, especially if they're not having prenatal care or their first ultrasound or a genetic diagnosis until later in the pregnancy. So certainly, options can be a little bit more limited. Um, and there may be more patients who are choosing a comfort care approach because termination wasn't something that they, um, were able to pursue, even if they were interested in it. Um, but we see families make all kinds of decisions, even if they came to us saying, this is what I want, sometimes we see them switching, um, to a different path for the pregnancy. We had one, question from the chat too, um, from Molly Casey. Um, she wanted to know if you're still seeing families being counseled by outside OB providers that comfort care is the only option, and if so, what is your general approach to handling that? Yeah, so, um, I think it's kind of a mixed bag for how the referrals come to us because sometimes patients are referred by their ref their OB or their MFM and so obviously, that would be an OB or an MFM who would have told them that we have the option for more um interventions or more aggressive care after delivery. And so in that situation, they would have been told that comfort care isn't the only option. But we also have some patients who self-refer to us, who were told by their OB that comfort care was really the only option available. Um, and that is something that we hear for a number of different diagnoses, not just trisomy 13 and trisomy 18. But even when I was in medical school, um, we still had teaching that trisomy 13 and trisomy 18 were a lethal diagnosis, and there were some babies that continued to live, but Um, it was always thought that patients who were, that these children who were living, um, beyond that first year of life were more likely mosaic. And so if you had a diagnosis of full trisomy 13 or 18, then they were not going to survive. But, um, I think we know a little bit more now that that's just not true, and that with more support, some of these kids can live longer even if they're not mosaic. And additionally, um, with respect to legislation changes, um, has that changed any genetic counseling practices? Um, I'm not aware of any restrictions on, um, a pregnancy interruption with the diagnosis of trisomy 13 and trisomy 18. I know that there are some states that, um, have limitations with the diagnosis of trisomy 21. Um, so I don't know that testing for trisomy 13 and 18 has changed because of that legislation, um, but potentially could be something that Is seen in the future. Yeah, I can add on to that a little bit too, as one of the genetic counselors who see these patients. You're right that there are certain states that have reasons bans or legislation in place that specifies specific reasons why termination of pregnancy may not be legal. In the case of Ohio, we have a ban that's um surrounding Down syndrome or trisomy 21, where a provider cannot perform a pregnancy termination if they know that there's trisomy 21 in the. fetus. And that does not specifically address, obviously, trisomy 13 or 18, but it has actually had some like domino effects for these patients. There are some clinics that their kind of legal interpretation has been to require an amniocentesis even for a high-risk cell-free DNA screen for trisomy 13 or 18 to confirm that it's not Down syndrome specifically and that it is involving a different chromosome. So that has added additional barriers and also kind of uncertainty for patients who may have heard about the Down syndrome band and we're not sure exactly how that um plays into something like trisomy 13 or 18. I was gonna ask, um, Doctor Hoffman as well, and sorry if you may have said this during your talk, but are there any specific like maternal morbidity complications that we see in higher rates in pregnancies with trisomy 13 or 18? I think about like placentas with chromosome abnormalities don't always do as well. And so do we see like higher rates of preeclampsia or abruption or other things that could be really impactful for the mother? Yeah, so rates of preeclampsia are higher in um pregnancies that have an abnormal placenta. And so in the vast majority of these cases, the placenta is also has trisomy 13 or trisomy 18. Um, and so there are higher chances of having high blood pressure for the mom. Really, the risk for a cesarean section is quite increased compared to baseline, and that can have a lot of morbidity and impact on future pregnancies, especially if a classical cesarean section is needed, meaning we have to cut up and down on the uterus rather than the. Typical low transverse because a classical um incision on the uterus doesn't heal as well as the low transverse, and it means that moms always need cesarean sections in the future and always need preterm cesarean sections in the future. So it can have an impact on future pregnancies, um, with that increased risk of C-section. Thank you. It looks like we also have a comment in the in the chat from Jacqueline Burton saying after hearing from Doctor Suar, it's interesting to note that patients receiving counseling, that comfort care is the only option, like we aren't being told that babies can still live for quite a while unexpectedly to the parents. And I think that's really insightful and I, I. I mean, I can't speak for all of us, but I think we have seen patients who've come to our fetal care center who are told to expect that their baby would pass away within hours. And then when we do their imaging, we don't actually see like a specific reason other than the diagnosis of anything that would be immediately life-threatening, and that is a big Kind of about face 180 for parents to now be expecting a different outcome for them. Um, looks like we have another question, Doctor Hoffman, and we do have some time, um, from Jiten Chang. Great presentation. Thank you. It sounds like it's a shared decision-making process for everything like continuous fetal monitoring and labor, crash C-section, etc. Are there any findings on ultrasound, mosaicism, or maternal comorbidities that would steer the counseling towards more or fewer interventions? Yeah, so if the size of the baby is appropriate for a vaginal delivery, then any interventions that the mom is OK with is something that we would support. So, um, ACOG or the American College of Obstetrics and Gynecology supports a cesarean section on maternal request, meaning if any mom says that they want a C-section, then that would be a reason to do a C-section, even if they've had vaginal deliveries before and there isn't really a fetal reason for it. And so we would apply that same principle to this diagnosis as well. So for some families, a live birth is the most important thing. And so in that situation, some families will choose to just have a C-section so that they can meet their baby alive without the concerns that um it may pass during labor. But for other families, decreasing their risk in future pregnancy is the most important thing. And so they will choose to have a vaginal delivery without monitoring and understand that baby may not be born alive. Um, The majority of the inductions that we have seen where we do an induction with no monitoring, the baby is still often born alive, um, and then if families decide that they want Interventions after or if they want to continue down a more completely comfort care approach is very much so part of the shared decision making. And also, we have families who sometimes change their mind multiple times during the pregnancy, even during the labor process. And so we're always keeping families updated on the information that we have about their pregnancy and trying to support their wishes and what's the right decision for their family. Have you seen what's worked well in terms of uh talking about this more than once or serially? For example, what you've covered is everything from the diagnosis, the implications of the diagnosis, and then trying to sort through, um, uh, family's wishes. What have you seen works best in terms of having discussions with family? Um, and we'll hear probably hopefully more about this with Doctor Henner later. Yeah. So the majority of the patients that we're seeing have already been counseled by their MFM. And so when we're seeing them, we're saying these are the things that we can offer. Does that sound like something that you would be interested in? And then most families aren't really ready to make a decision after that initial meeting, and they may have some ideas of this is where we really would like to go. But at every single one of their prenatal appointments, we're checking in on the most recent ultrasound findings, how mom is doing from a blood pressure standpoint, from preterm labor standpoint, and continuing to adjust, um, if continuing to do non-stress tests is in their best interest, or is it more stressful for them and they want to take a break from them for a little bit. And it's also a common thing for families to ask, can I take a vacation, um, during this time? Um, and it's something that I've seen in more like social media things, families who want to do a bucket list for their baby, and so they'll want to do more traveling, um, so that their baby can see these things, um, before delivery, because they may not have that opportunity after delivery. And so we'll also sometimes take a pause on the antenatal testing so that they can, um, do something that's important to them, and then kind of come back. All right. I'm seeing another question here from Kirsten Reimer. Um, can we speak to the frequency of false positive or false negative results of NIPT, and has, has it decreased since NIPT first became available, and can we speak to the impact of inaccurate results on families? I'm happy to comment on that unless you would like to as well, OK, um, so yes, I would say overall, things have probably changed a little bit since NAPT was first introduced onto the market as the laboratories have been improving their algorithms and their testing strategies. So the actual technical sensitivity and specificity has always been fairly good, um, for both of these conditions, although NIPT performs best for trisomy 21, then a little bit less for rice 18, and then a little bit less for TRC 13, um. Part of that is technical, but actually a lot of that comes from just the actual mathematical calculation for things like the positive predictive value incorporate the prevalence of disease, and we know that trisomy 13 is the most rare, and then trisomy 18 is a little less rare, and then trisomy 21 is the most common. So some of the false negatives and positives are purely kind of statistical, um, given that it's a screening test. Although, I would hazard a guess that if we were to test all placentas of patients who have quote-unquote false positive NIPT, I bet we would find abnormal cells within the placentas, whether or not it's like full confined placental mosaicism or if there's mosaicism within the placenta itself, since NIPT is really testing free placental DNA, not fetal DNA. And so it does present a Challenge when counseling patients because you have to explain like most of the time the placenta is the same as the fetus when it comes to the chromosomal makeup, but not always. And what we are really caring about really for the long-term prognosis is whether the fetus has these chromosome conditions. Um, the NIPT test that you had is really testing your placenta and certainly has implications, but in a different way. So, long answer to the question that, yes, I think the test has gotten a little bit better, but some of it is not specifically related to technical factors, but just kind of the specifics of um the statistics. And then your second part of that question was the impact of inaccurate results on families. Um, obviously, it's huge, right? So false positive results are extremely stressful. NIPT is often happening sort of in this gray zone between getting um, Having the availability to do a CVS and having to wait for an amniocentesis. So patients may be getting results kind of at the end point of when you can do a CVS and then have to wait a few weeks to get the amniocentesis, so they're living within this period of uncertainty that we can't resolve for a while. And then there's debates about whether or not CVS is always the best test to confirm these, given that we've already tested placental DNA or screened placental DNA with this, and are we just gonna pick up on mosaicism. That we're still gonna recommend an amniocentesis for. So I think it causes this diagnostic odyssey to start very early in a patient's pregnancy and cause a lot of stress at a time when we can do ultrasounds, but we can't necessarily see all the details that we want. And so unless you're seeing something like a large cystic fibroma, for example, we may not be able to use ultrasound to help refine our risk assessment. So, That is challenging, and then false positives obviously cause this rebound effect of doing an amniocentesis, confirming normal chromosomes in a fetus, and the parents having to kind of come down from all that anxiety. Um. False negatives, I'm sure are challenging. I don't see those as often, though we have certainly seen them in particular and where we are seeing patients and patients who have anomalies that are suggestive of one of these conditions and we're reassured by their NIPT results, but then have to do an amniocentesis and confirm that there was a false negative result. That is also understandably very concerning and difficult for patients. Um, I'm not sure, Doctor Hoffman, do you have anything to add on that? Yeah, just that we have seen false negatives and We do recommend the amniocentesis to confirm. And if we do have a patient who has um a high-risk NIPT but then a low-risk amnio, I do still recommend growth scans in the 3rd trimester for those patients, just because if there is a placental impact with different genetics, it can impact the growth of the baby. Well, thanks so much for that, uh, discussion.